Applicant: The applicant, Dawn A. Lowe, is a physiologist whose research is focused on molecular mechanisms underlying age-induced deterioration of muscle. Although trained in muscle physiology, Dr. Lowe has acquired experience in muscle biochemistry and molecular biology, and in the current application proposes to learn and utilize molecular biophysical techniques to round out a multidisciplinary approach to be used in studying aging muscle. Her career goal is to develop a) an independent line of research in an academic setting, b) an extramurally-funded laboratory and c) mentoring skills needed to guide graduate students and post-doctoral fellows in research and academia. The Mentored Research Scientist Development Award will provide the necessary support and training for the applicant to reach these career goals. Career Development/Training Plan: The primary element of the plan will be the acquisition of advanced molecular biophysical techniques from mentored training. The majority of the training will come from the sponsor but key mentoring will also be obtained from an advisory committee composed of established investigators in the fields of biophysics and aging. Structured activities for further career and research development will include attendance at a summer research workshop on aging, formal course work, attendance and participation at national scientific meetings, regular involvement in journal clubs and seminars, and continued affiliation with The Center on Aging and The Center for Muscle and Muscle Disorders at the University of Minnesota. Research Plan: The overall aim of this proposal is for the Dr. Lowe to learn and apply molecular biophysical techniques to explore age-related alterations in muscle contractility. A decline in muscle function is a common yet undesired consequence of aging and in order to establish methods to reverse or prevent the decline, the underlying molecular mechanisms must first be elucidated. Dr. Lowe will use electron paramagnetic resonance spectroscopy (Aim 1) and single molecule biophysical (Aim 2) techniques to study the effects of age on the structure, function, and interaction of two fundamental contractile proteins in muscle, myosin and actin. Environment: The environment for Dr. Lowe's training plan is outstanding. The sponsor, Dr. David Thomas, is an internationally known scientist in the field of muscle biophysics, is on the Board of Directors for both of the Centers mentioned above, and is the director of two NIH-funded training programs, one in muscle and the other in biophysics.